T Cell Phenotypes in Amyotropic Lateral Sclerosis (ALS), Influence of Vitamin D

NCT ID: NCT02756104

Last Updated: 2020-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-07
• Study Completion Date: 2020-05-25

Brief Summary

ALS is a devastative disorder characterized by motor neuron degeneration. Median survival is 3 years after onset, but may vary from a few months to more than 30 years. Various factors have been suspected to play a role in such a variation, but recently, it has been described that regulatory T-lymphocytes (T regs) may mediate ALS progression and survival. Vitamin D is an hormone know to regulated T reg function in vivo and in vitro. It have recently demonstrated that vitamin D (VD) levels correlated with ALS prognosis. The investigator want to go further in the study of the immune processes that could modulate prognosis in ALS. This could allow proposing VD as a potential treatment of ALS in a future trial. More largely, this could reinforce arguments in favor of an immune intervention to attenuate the severity of this devastating disorder.

Detailed Description

ALS is a devastative disorder characterized by motor neuron degeneration. Median survival is 3 years after onset, but may vary from a few months to more than 30 years. Various factors have been suspected to play a role in such a variation, but recently, it has been described that regulatory T-lymphocytes (T regs) may mediate ALS progression and survival. Vitamin D is an hormone know to regulated T reg function in vivo and in vitro. It have recently demonstrated that vitamin D (VD) levels correlated with ALS prognosis and patients with a severe VD deficiency had a 6 time more rapid evolution than those with normal VD levels. The investigator want to go further in the study of the immune processes that could modulate prognosis in ALS. We propose 1- to study T cell phenotypes (Treg, CD4 (cluster of differentiation 4) -Th1, -Th17, -Th2, CD8 (cluster of differentiation 8)and NK) in ALS vs controls ; 2- In VD-deficient patients, to analyze the influence of a vitamin D supplementation on T cell phenotypes ; 3- to study the relationships between T cell phenotypes and ALS prognostic factors. The project will include 70 ALS patients and 27 controls in this prospective study. VD-deficient patients will be supplemented, according to national recommendations for 6 months, and the evolution of T cell phenotypes will be followed over 1 year. We hope to demonstrate first that T cell phenotypes in ALS are consistent with a pro inflammatory profile, compared to controls, secondly that VD treatment modulates T cell phenotypes towards a non-inflammatory one and, thirdly, that inflammatory T cell phenotypes correlate with a worse prognosis of the disease. This could allow proposing VD as a potential treatment of ALS in a future trial. More largely, this could reinforce arguments in favor of an immune intervention to attenuate the severity of this devastating disorder.

Conditions

ALS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Volunteers

Healthy People on each collecting blood for phenotyping Tcells

Group Type: OTHER

phenotyping Tcells

Intervention Type: OTHER

Collecting blood for analyses of the T cells phenotypes

Patients with ALS

Patients with ALS deficient or not in Vitamin D on each collecting blood for phenotyping Tcells.

The patients who are deficient in Vitamin D will have supplementation in vitamin D

Group Type: OTHER

phenotyping Tcells

Intervention Type: OTHER

Collecting blood for analyses of the T cells phenotypes

Supplementation in vitamin D

Intervention Type: OTHER

Supplementation in vitamin D for the patients who are deficient on vitamin D

Interventions

phenotyping Tcells

Collecting blood for analyses of the T cells phenotypes

Intervention Type: OTHER

Supplementation in vitamin D

Supplementation in vitamin D for the patients who are deficient on vitamin D

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Man or woman with sporadic ALS and a possible, probable or definite diagnosis regarding the revised Escorial criteria (Forbes et al., 2001). Patients are followed quarterly according to national recommendations. At the end of the follow up period (1 year for each patient), all patients remaining in the " possible " group of diagnosis will be excluded.
• Disease onset (date of onset of muscle weakness) < 18 months at the time of inclusion.
• Age: 30 to 80 years-old, inclusive.
• Patient treated by riluzole at a steady dosage since at least 3 months.
• Patient accepting to give informed consent

•Subject accepting to give informed consent

Exclusion Criteria

• A previous treatment with VD in the preceding 2 years, whatever the dose used.
• Patient with an already known autoimmune disorder
• Patient with severe ALS involvement suggesting that survival over the 1 year follow up is highly unlikely (ex : tetraplegia, use of non-invasive ventilation for more than 10 hrs/day, ALSFRS-R (ALS Functional Rating Scale) score < à 20).
• Pregnant or breast-feeding woman.
• Patient without social security insurance

For the Controls:

• Subject with an already known neurodegenerative disorder
• Subject with an already known autoimmune disorder
• Subject who received a treatment with VD in the preceding 2 years, whatever the dose used.
• Pregnant or breastfeeding woman
• Subject without social security insurance

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ARSLA

UNKNOWN

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William CAMU, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Locations

University Hospital of Montpellier

Montpellier, , France

Countries

France

Other Identifiers

9632

Identifier Type: -

Identifier Source: org_study_id